The goal os this program project is to develop approaches for gene therapy for the beta-chain hemoglobinopathies: sickle cell anemia and homozygous beta-thalassemia. The program consists of five projects and four core units. The objective of this project is to develop vectors that will result in the production of therapeutic levels of fetal hemoglobin in the red cell progeny of transduced stem cells. The next projects focus on the development of new vector technologies for stem cell gene therapy: foamy viral vectors and deleted adeno AAV vectors. Success in the development of these new vectors will have a major impact on the field of stem cell gene therapy. The next project uses a new technology, based on chemical inducers of dimerization to achieve in vivo selection of genetically modifier stem cells. The final project studies oncoretroviral and lentiviral vectors in the baboon model and attempts new approaches for improving stem cell transduction. Unit A is a SCID/NOD mice unit and will assist investigators in the assessment of gene transfer into human stem cells. Unit B will assist the projects with cell biology and globin expression studies. Unit C will perform bone marrow transplantation in baboons to assess gene transfer into the stem cells of primates. Unit D will provide administrative support.